The overall goal of the candidate's research program is to define the genetic and non-genetic factors that determine the variability in human vascular response, both between individuals, and between ethnic groups. The investigator has previously shown marked interethnic differences in vascular response with attenuated beta-adrenergic and nitric oxide-mediated vasodilation and increased alpha-adrenergic vasoconstriction in African-Americans. Three related but separate projects are currently underway that extend these observations: 1) Ethnic differences in autonomic cardiovascular control comprises a series of studies designed to define and localize the mechanisms, including the relationship between psychological traits and sympathetic activity, which regulate vascular response in different ethnic groups. 2)"Modulation of adrenergic response by estrogen" comprises a series of studies designed to probe central and peripheral components of adrenergic control in a targeted fashion to define the level(s) at which estrogen produces effects and to compare responses in African-American and Caucasian women. The effects of estrogen on basal sympathetic activity, stimulated sympathetic activity, central sympathoinhibition, presynaptic sympathetic regulatory mechanisms, postsynaptic vascular responsiveness and the effects on salt sensitivity will be all determined. 3) "Genetic variability and vascular response" a project described in detail in this proposal has the overall aim of defining the role of genetic factors in the determination of vascular response through the study of individuals selected on the basis of genotype. We will examine the hypothesis that functionally significant polymorphisms of beta2-adrenoceptor, alpha1-adrenoceptor and endothelial nitric oxide synthase genes alter vascular response in humans. Thus, the present proposal embraces three concurrent, conceptually linked, projects that define genetic and non-genetic factors regulating human vascular response and will allow the investigator to continue to pursue a highly productive, patient oriented research career and focus on the long-term goal of understanding the mechanisms that regulate vascular response and how these differ between ethnic groups, both in health and disease. The unique research environment, the established ongoing research program and the investigator's commitment to mentoring will allow him to continue to contribute to the fostering of clinical research through the training of young clinical investigators.